Lip and oral cavity tumors

ISSN 2595-2544 CASE REPORT Oral paracoccidioidomycosis affecting the buccal mucosa

João Vitor Rocha Silva1, John Lennon Silva Cunha2, Amanda Feitoza da Silva1, Allan Ulisses de Carvalho Melo3, Ricardo Luiz Cavalcanti de Albuquerque-Júnior4

Abstract Paracoccidioidomycosis (PCM) is a disease caused by the Paracoccidioides brasiliensis, common in Brazil and in some other areas of Latin America. We report a case of a 50-year-old male patient, farm worker, smoker, presenting with ulcerated lesion with moriform appearance in the left buccal mucosa. The patient underwent incisional and diagnosed with PCM. He was referred to the infectologist for treatment of the lesion. Although PCM primarily affects the lungs, it is often diagnosed through oral manifestations. Thus, dentists play a fundamental 1Universidade Tiradentes (UNIT), Departamento de Odontologia, role in the identification of these lesions and referral for appropriate treatment. Aracaju, SE, Brasil Keywords: diagnosis, oral; oral manifestations; paracoccidioidomycosis. 2Universidade Estadual de Campinas (UNICAMP), Faculdade de Odontologia de Piracicaba, Departamento de Diagnóstico Oral, Área de Patologia Oral, Piracicaba, SP, Brasil Introduction 3Centro Universitário Ages (AGES), Paripiranga, AL, Brasil Paracoccidioidomycosis (PCM), also known as South American , is 4Universidade Tiradentes (UNIT), a tropical disease caused by the Paracoccidioides brasiliensis, Instituto de Tecnologia e Pesquisa, initially described by Adolfo Lutz in 19081,2. Although a rare disorder from a Laboratório de Morfologia e Patologia Experimental, Aracaju, SE, Brasil global perspective, the disease is endemic in Latin America and is estimated to infect about 10 million Latin Americans. In Brazil, PCM is the main cause of death by systemic , and the eighth cause among infectious diseases1,3, Financial support: None. Conflicts of interest: No conflicts with an estimated incidence of approximately 1 to 3.7 cases per million of interest declared concerning individuals annually1. the publication of this article. Submitted: January 12, 2019. PMC more commonly affects farm workers and/or people who live in rural Accepted: March 27, 2019. The study was carried out areas, particularly males, smokers and/or chronic alcoholics, aged between at Universidade Tiradentes 30 and 50 years2,3. Although the primary route of PCM infection is pulmonary, (UNIT), Aracaju, SE, Brasil. the disease is often diagnosed by oral manifestations4. Oral mucosal lesions The abstract was presented at the 44th Brazilian Congress of Oral Medicine and may be the first visible clinical manifestation of the disease, often even Oral Pathology, Rio de Janeiro, RJ, Brasil. preceding lung lesions1. The oral cavity may be affected at one or multiple sites, with the gingiva/alveolar ridge and palate being the most frequent anatomical sites1,2. Classic clinical presentations are granular, erythematous or ulcerated lesions, with irregular borders and moriform appearance2,5. Copyright Silva et al. This is an Open Access article distributed under the Furthermore, of PCM oral lesions are still uncommon in routine terms of the Creative Commons dentistry1, which leads to many cases being diagnosed late, causing serious Attribution License, which permits unrestricted use, distribution, damage to the patient. Thus, dentists play a fundamental role in the diagnosis and reproduction in any medium, of these lesions and referral for appropriate treatment5. Herein, we report provided the original work is properly cited. a case of PMC in buccal mucosa.

Silva et al. Arch Head Neck Surg. 2018;47(4):e20190109. DOI: 10.4322/ahns.2018.0109 1/5 Oral paracoccidioidomycosis affecting the buccal mucosa Lip and oral cavity tumors

Case report A 50-year-old male was referred to a private clinic for evaluation of a painless lesion on the buccal mucosa. Extraoral examination was unremarkable. The intraoral examination revealed an ulcerated lesion with moriform appearance in the left buccal mucosa, measuring approximately 2.0 cm in diameter (Figure 1A), and uncertain time of evolution. No other symptoms were present. The patient worked in farming, and that he was smoker and alcohol drinker. Considering all clinic features, a provisional diagnosis of PCM was established and an incisional biopsy was performed. Macroscopic examination revealed two fragments of fibrous soft tissue, yellowish in color, and with an irregular surface (Figure 1B). Microscopic examination of HE-stained histological slices revealed a fragment of oral mucosa lined by parakeratinized stratified squamous epithelium exhibiting acanthosis, exocytosis, spongiosis, and pseudoepitheliomatous hyperplasia. The lamina propria consisted of dense connective tissue, with an intense non-caseiform granulomatous inflammatory reaction, with the formation of numerous epithelioid histiocytes and Langhans giant cells (Figure 1C, 1D, and 1E). Histological sections stained in Grocott showed the presence of rounded , organized singly or forming multiple buds that resemble images classically described as “rudder wheel” or “Mickey mouse head”, interpreted as yeasts of Paracoccidioides brasiliensis (Figure 1F and 1G). The diagnosis was PCM. The patient was referred to the infectologist for proper management of the lesion.

Discussion PMC more commonly affects farm workers and/or people who live in rural areas, particularly males in the ratio of 15:1, smokers and/or chronic alcoholics, aged between 30 and 50 years2,4,5. This unequal distribution has been attributed to two main factors, namely: 1) the greater exposure of men to soil and 2) the role of estrogen, which inhibits the transformation of the mycelial form of the microorganisms to the form, which is pathogenic2,4. These factors corroborate with the case reported here since the 50 years old patient was a smoker for over thirty years, alcoholic and worked in rural areas. Most cases of PCM begin with pulmonary involvement after exposure to spores4. Inhalation of P. brasiliensis leads to infection even without manifestation of active disease2. The development of the disease depends on the virulence of the microorganism and the hormonal, genetic, nutritional, and immune conditions of the individual2,4. There may also be reactivations of latent foci. The latency period is quite variable, having been reported up to 60 years for the manifestation of the disease1. The clinical classification of infection includes /subacute (juvenile), chronic, and residual forms. The acute form is characterized by depression of the immune cellular response with low levels of IFN-γ production4,5. It usually affects young men and women, compromising liver, spleen, bone marrow, and lymph nodes2. The chronic form is much more common in men over 30 years of age, and its development is slow and gradual, affecting a single organ (unifocal) or several organs or systems (multifocal)1,5. Lung lesion is usually bilateral and symmetrical, giving a “butterfly wing” appearance in

Silva et al. Arch Head Neck Surg. 2018;47(4):e20190109. DOI: 10.4322/ahns.2018.0109 2/5 Oral paracoccidioidomycosis affecting the buccal mucosa Lip and oral cavity tumors

Figure 1. (A) Clinical aspect of the lesion. Multiple finely granular hemorrhagic pinpoint erosions with a mulberry-like appearance presented in the left buccal mucosa; (B) Macroscopic appearance of surgical specimens; (C, D, and E) Histological features of oral paracoccidioidomycosis; (C) The overlying mucosa showing pseudoepitheliomatous hyperplasia and an intense subepithelial inflammatory infiltrate; (D) Ovoid yeasts with birefringent membrane were also evidenced (arrows); (E) Non-caseiform granulomatous inflammatory reaction, with the formation of numerous epithelioid histiocytes and multinucleated giant cells (hematoxylin and eosin stain); (F and G) Grocott-stained sections showing the presence of microorganisms exhibiting multiple buddings (ship’s wheel appearances) (F) and double buddings (Mickey Mouse ears) (G).

radiographic imaging2. The central and basal regions of the lungs can be affected, and the apex is usually spared3. Oral lesions frequently appear in the chronic form of PCM1,2. Clinically, the lesions are infiltrative, ulcerated, and with a moriform aspect. The anatomical sites most involved are the gingiva/alveolar ridge, tongue, palate, buccal mucosa, and lips1-3. Often, one or multiple sites of the oral cavity may be affected1,5. The nonspecific clinical presentation of PMC makes differential

Silva et al. Arch Head Neck Surg. 2018;47(4):e20190109. DOI: 10.4322/ahns.2018.0109 3/5 Oral paracoccidioidomycosis affecting the buccal mucosa Lip and oral cavity tumors

diagnosis wide, including a spectrum of benign lesions, potentially malignant and malignant, with distinct biological behaviors. Squamous cell carcinoma, traumatic ulcer, , oral , sarcoidosis, Wegener’s granulomatosis, leishmaniasis, actinomycosis, and primary syphilis are some of the lesions that may have similar clinical characteristics2.

The diagnosis of PCM is based on the identification of P. brasiliensis by histopathological examination or exfoliative cytology5. Histologically, lesions are represented by a fragment of oral mucosa lined by parakeratinized stratified squamous epithelium, which exhibits pseudoepitheliomatous hyperplasia and ulcerated areas1,2,5. The lamina propria is characterized by the presence of chronic granulomatous inflammation, rich in epithelioid macrophages and multinucleated giant cells, but usually without central necrosis1,2. The fungi appear as spherical structures with sizes ranging from 2 to 30 μm and may be dispersed by the inflammatory infiltrate or within multinucleated giant cells1. These yeasts can be identified by the Hematoxylin-Eosin staining technique, or more easily by special staining methods such as periodic acid–Schiff (PAS) and Grocott-Gomori2,5. Spore-forming microorganisms are sometimes seen, conferring a “Mickey ear” or “rudder” appearance; this data also coincides with our findings2,4.

The main treatment options are sulfamide derivatives, trimethoprim, , azole derivatives, and terbinafine2,3,5. Treatment is always prolonged, and careful follow-up of the patient is necessary, even when “clinical cure” is achieved, due to the possibility of reactivation of the fungus. If not treated properly, PMC can be fatal2,5.

In summary, PMC is an endemic and systemic disease. Although the primary route of infection is pulmonary, by inhalation of spores or fungal particles, several anatomical sites may be affected by lymphohematogenous dissemination, including the buccal mucosa. Thus, dentists play a fundamental role in the identification of these lesions, in the correct diagnosis and referral to the appropriate treatment. Careful clinical evaluation and complementary exams, such as exfoliative cytology and incisional biopsy, are valuable procedures in the diagnosis of this disease.

References 1. Arruda JAA, Schuch LF, Abreu LG, Silva LVO, Mosconi C, Monteiro JLGC, Batista AC, Hildebrand LC, Martins MD, Sobral APV, Rivero ERC, Gomes APN, Silva TA, Vasconcelos ACU, Mesquita RA. A multicentre study of oral paracoccidioidomycosis: analysis of 320 cases and literature review. Oral Dis. 2018;24(8):1492-502. http:// dx.doi.org/10.1111/odi.12925. PMid:29949225.

2. Albuquerque AD NO, Araújo AVA, Cerqueira DA, Cesconetto LA, Provenzano N, Oliveira EMF. Diagnosis and treatment of paracoccidioidomycosis in the maxillofacial region: a report of 5 cases. Case Rep Otolaryngol. 2018;1524150:1524150. http://dx.doi.org/10.1155/2018/1524150. PMid:29850333.

Silva et al. Arch Head Neck Surg. 2018;47(4):e20190109. DOI: 10.4322/ahns.2018.0109 4/5 Oral paracoccidioidomycosis affecting the buccal mucosa Lip and oral cavity tumors

*Correspondence 3. Dutra LM, Silva THM, Falqueto A, Peçanha PM, Souza LRM, Gonçalves SS, Velloso John Lennon Silva Cunha TRG. Oral paracoccidioidomycosis in a single-center retrospective analysis from Universidade Estadual de Campinas (UNICAMP), Faculdade de Odontologia a Brazilian southeastern population. J Infect Public Health. 2018;11(4):530-3. de Piracicaba, Departamento de http://dx.doi.org/10.1016/j.jiph.2017.10.009. PMid:29153538. Diagnóstico Oral, Área de Patologia Oral 4. Shikanai-Yasuda MA, Mendes RP, Colombo AL, Telles FQ, Kono A, Paniago AMM, Av. Limeira, 901, CP 52, Nathan A, Valle ACF, Bagagli E, Benard G, Ferreira MS, Teixeira MM, Vergara CEP 13414-903, Piracicaba (SP), Brasil MLS, Pereira RM, Cavalcante RS, Hahn R, Durlacher RR, Khoury Z, Camargo ZP, Tel.: +55 (79) 99654-0805 E-mail: [email protected] Moretti ML, Martinez R. II Consenso Brasileiro em Paracoccidioidomicose - 2017. Epidemiol Serv Saúde, 27, n. spe, e0500001, 2018. http://dx.doi.org/10.5123/ Authors information s1679-49742018000500001. JVRS and AFS - Dentists, Universidade Tiradentes (UNIT); JLSC - Dentist, 5. Neves-Silva R, Fernandes PM, Santos-Silva AR, Vargas PA, Souza Cavalcante R, MSc student, Universidade Estadual Lopes MA. Unusual intestinal involvement by paracoccidioidomycosis diagnosed de Campinas (UNICAMP); RLCAJ - after oral manifestation. Mycopathologia. 2018;183(6):987-93. http://dx.doi. Dentist, PhD, Universidade Tiradentes (UNIT); AUCM - Dentist, PhD, Centro org/10.1007/s11046-018-0250-0. PMid:29453699. Universitário Ages (AGES).

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